title: Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe/USA: genetic and clinical studies of 86 unrelated patients with low-molecular-weight proteinuria.
abstract: Dent disease is an X-linked disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called 'low-molecular-weight proteinuric disease', have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly identical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.
authors.affiliation: Department of Pediatrics, Ohashi Hospital, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
authors.forename: Fusako
authors.initials: F
authors.lastname: Komoda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Miura
authors.forename: Junko
authors.initials: J
authors.lastname: Takita
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Shimadzu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Akira
authors.initials: A
authors.lastname: Ashida
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D057973:Dent Disease / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011507:Proteinuria / Q000209:etiology* / Q000235:genetics / Q000652:urine; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C097503:CLC-5 chloride channel; D018118:Chloride Channels; D004247:DNA; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human
keywords: CLCN5; Japanese Dent disease; Lowe syndrome; OCRL1; dent disease; low-molecular-weight proteinuria